Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease characterised by the deposition of misfolded proteins in the motor cortex and motor neurons. Although a multitude of ALS-associated mutated proteins have been identified, few have been linked to exosomes, a form of extracellular vesicles involved in inter-cellular communication. Additionally, the role of exosomes in ALS is undetermined, specifically in relation to pathogenic stress granule formation, a response to cellular stress involving aggregation of non-coding RNAs and their RNA binding proteins. Therefore, this study aimed to determine the proteome of brain derived exosomes (BDEs) isolated from ALS subjects and identify novel ALS-associated deregulated proteins and their potential contributions to pathogenic pathways in ALS. BDEs were isolated from human post-mortem ALS (n=10) and control (n=5) motor cortex brain tissues through a novel ultracentrifugation protocol (1). Following thorough characterisation, BDEs successfully met the minimum criteria required by The International Society for Extracellular Vesicles to be classified as exosomes (2). The BDEs’ protein content subsequently underwent mass spectrometry analysis, allowing for a panel of novel ALS-associated proteins to be identified. This panel consisted of 16 statistically significant differentially packaged proteins identified in the ALS BDEs compared to the control BDEs. This included several up-regulated RNA binding proteins which were determined through pathway analysis to be associated with stress granule dynamics. The identification of these RNA binding proteins in the ALS BDEs suggests there may be a relationship between ALS-associated stress granules and ALS BDE packaging, highlighting a potential role for exosomes in the pathogenesis of ALS.